chr2-165183208-G-A

Variant names:

• chr2-165183208-G-A
• rs2165179
• NM_006922.4:c.-51+3343C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006922.4(SCN3A):​c.-51+3343C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,150 control chromosomes in the GnomAD database, including 1,727 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.11 (1727 hom., cov: 32)
• Consequence: SCN3A NM_006922.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.51
• Publications: 1 publications found

Genes affected

SCN3A (HGNC:10590): (sodium voltage-gated channel alpha subunit 3) Voltage-gated sodium channels are transmembrane glycoprotein complexes composed of a large alpha subunit with 24 transmembrane domains and one or more regulatory beta subunits. They are responsible for the generation and propagation of action potentials in neurons and muscle. This gene encodes one member of the sodium channel alpha subunit gene family, and is found in a cluster of five alpha subunit genes on chromosome 2. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

SCN3A Gene-Disease associations (from GenCC):

• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: Illumina, ClinGen
• developmental and epileptic encephalopathy, 62

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• epilepsy, familial focal, with variable foci 4

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000236283 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN3A	NM_006922.4	c.-51+3343C>T		intron_variant	Intron 2 of 27	ENST00000283254.12	NP_008853.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN3A	ENST00000283254.12	c.-51+3343C>T		intron_variant	Intron 2 of 27	1	NM_006922.4	ENSP00000283254.7

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16620 AN: 152032 Hom.: 1710 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.0813

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.0475

Gnomad EAS AF: 0.479

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.0534

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0416

Gnomad OTH AF: 0.130

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.109 AC: 16656 AN: 152150 Hom.: 1727 Cov.: 32 AF XY: 0.115 AC XY: 8583 AN XY: 74382

African (AFR) AF: 0.140 AC: 5818 AN: 41518

American (AMR) AF: 0.254 AC: 3879 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0475 AC: 165 AN: 3472

East Asian (EAS) AF: 0.479 AC: 2462 AN: 5138

South Asian (SAS) AF: 0.112 AC: 541 AN: 4824

European-Finnish (FIN) AF: 0.0534 AC: 566 AN: 10604

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0416 AC: 2829 AN: 68010

Other (OTH) AF: 0.141 AC: 296 AN: 2106

Alfa AF: 0.0786 Hom.: 202

Bravo AF: 0.132

Asia WGS AF: 0.307 AC: 1062 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	9.0
DANN	Benign	0.59
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2165179; hg19: chr2-166039718;